Pertussis toxin (PTx) has various effects in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). This study was designed to explore the protective effects of PTx of different doses and subunits. EAE model was induced with myelin oligodendrocyte glycoprotein (MOG35-55, 200 ug) plus complete Freund’s adjuvant in 6-7 week-old female C57BL/6 mice. PTx reduced clinical deficits of EAE by 91.3%. This reduction in clinical deficits was achieved by attenuating demyelination by 75.5%. Furthermore, PTx reduced the lymphocyte infiltration, deactivated microglia activation and changed T cell profile by increasing T helper (type 1 and 2) and T regulatory cells.